title: Blockade of dopamine D1-like receptor signalling protects mice against OVA-induced acute asthma by inhibiting B-cell activating transcription factor signalling and Th17 function.
abstract: Previous studies have consistently demonstrated that dopamine D1-like receptor (D1-like-R) signalling is implicated in the pathogenesis of experimental autoimmune encephalomyelitis and type I diabetes. Given that allergic asthma shares certain disease aetiology similarities with autoimmune diseases, we conducted studies in OVA-induced mice aiming to address the impact of D1-like-R signalling on the pathogenesis of allergic asthma. It was noted that blockade of D1-like-R signalling provided protection for mice against OVA-induced acute asthma. Particularly, treatment of OVA-induced mice with SCH23390, a D1-like-R antagonist, significantly attenuated inflammatory infiltration in the airways along with repressed goblet cell hyperplasia and mucus production, as well as airway resistance. By contrast, administration of SKF83959, a D1-like-R agonist, displayed the opposite effect. Blockade of D1-like-R signalling impaired Th17 function, as manifested by a significant reduction of Th17 cells in the spleen and bronchoalveolar lavage fluid. Mechanistic studies revealed that D1-like-R signalling enhances B-cell activating transcription factor activity, which then transcribes the expression of RORγt, a Th17 transcription factor; accordingly, D1-like-R signalling regulates Th17 differentiation to promote the development of allergic asthma. Taken together, the data obtained in the present suggest that blockade of D1-like-R signalling could be an effective therapeutic strategy for the prevention and treatment of allergic asthma in clinical practice.
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China; Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Subo
authors.initials: S
authors.lastname: Gong
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Li
authors.forename: Libing
authors.initials: L
authors.lastname: Ma
authors.forename: Keng
authors.initials: K
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Guyi
authors.initials: G
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ji
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Ruoyun
authors.initials: R
authors.lastname: Ouyang
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
authors.forename: Xudong
authors.initials: X
authors.lastname: Xiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000208:Acute Disease; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050976:Basic-Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D001552:Benzazepines; D034741:RNA, Small Interfering; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D010047:Ovalbumin; D004298:Dopamine
keywords: B-cell activating transcription factor; Th17 cells; asthma; dopamine D1-like receptor